Analgesia Using Transcutaneous Electric Nerve Stimulation in Office Bladder Chemodenervation, a Randomized Controlled Trial.

IMPORTANCE: Office bladder chemodenervation, performed via cystoscopy with intradetrusor onabotulinumtoxinA (BOTOX) injections, is a common treatment for overactive bladder/urge urinary incontinence. Transcutaneous electric nerve stimulation (TENS) has shown to provide analgesia during office hysteroscopy. Adjuvant analgesia using TENS during bladder chemodenervation has not been studied. OBJECTIVE: The primary outcome is a clinically significant (10-mm) difference in pain visual analog scale (VAS) measurements during injections for chemodenervation using active TENS compared with placebo TENS. We hypothesize that active TENS use will significantly change pain VAS scores. Secondary outcomes include 5-point pain Likert scale, satisfaction 10-point scale, and adverse events. STUDY DESIGN: This was a double-blind randomized control trial of men and women with urinary urge incontinence undergoing office chemodenervation performed in an academic and private setting. Participants were randomized into 2 groups: chemodenervation with active TENS or placebo TENS. Power calculation determined 100 patients would be required detect a difference of 10 mm on pain VAS. RESULTS: One hundred one (85 female and 16 male) participants were recruited. No differences were noted in the demographics. Participants in the active TENS group reported a difference of greater than 10 mm in pain VAS scores (48 ± 23 vs 31 ± 23, P = 0.01). Satisfaction index scores were high but no difference was noted between groups (8.6 vs 8.7, P = 0.68). CONCLUSIONS: Most participants were eligible to use TENS units. Transcutaneous electric nerve stimulation is a safe and noninvasive adjuvant analgesia option for patients undergoing this procedure. Lower pain levels and high satisfaction rates suggest that this is an additional analgesic option during outpatient chemodenervation.

Examining reasons that patients discard cryopreserved oocytes.

PURPOSE: Assess the rate, rationale, and characteristics of patients who cryopreserved and subsequently discarded their oocytes, and compare their characteristics to patients with continued cryopreservation of oocytes. METHODS: All patients who disposed of cryopreserved oocytes between 2009 and 2022 reported their reason for discarding their oocytes. This was a retrospective cohort study. RESULTS: Of 5,010 patients who underwent oocyte cryopreservation (OC) cycles, 201 (4%) patients elected to discard their oocytes and 751 (15%) thawed oocytes for clinical use. The average ages of OC and disposal were 35 and 39 years old, respectively. Of the 201 patients who discarded their oocytes, 71 patients (35%) requested disposal after having a child. Twenty-six (13%) discarded oocytes because of worsening cancer and three (1.4%) discarded because of death. 16 (8%) discarded oocytes due to cost of cryopreservation and eight (4%) due to low oocyte yield. Ten (5%) patients underwent new IVF cycles and discarded previously stored oocytes. Sixty-seven patients (33%) discarded oocytes for unspecified reasons. When comparing patients who discarded oocytes with those who did not, the former had lower AMH (2.7 vs 3.5 ng/ml, p < 0.001) but otherwise comparable age and number of cryopreserved oocytes. The mean age for those with continued cryopreservation was 35.4 years at time of OC and 40 years at time of data collection in June 2023. CONCLUSION: Childbirth was the most common reason to dispose of oocytes followed by unspecified reasons. Larger studies of oocyte disposal may better define clinical characteristics of patients most likely to use, maintain or discard their oocytes.

Views of parents of children with sickle cell disease on pre-implantation genetic diagnosis.

Pre-implantation genetic diagnosis (PGD) is an option for parents who have a child with sickle cell disease (SCD) to have another child without SCD. We conducted a survey of 19 parents with at least one child with SCD to investigate views on PGD. Before education, 44% of parents were aware of PGD. All parents rated PGD education as important. All parents considering another child also reported interest in using PGD if insurance covered its costs. Parents who have a child with SCD appear to be interested in PGD and educational tools informing this group about PGD should be developed.

Cautery artifact understages urothelial cancer at initial transurethral resection of large bladder tumours.

INTRODUCTION: We sought to determine how frequently cautery (thermal) artifact precludes an accurate determination of stage at initial transurethral resection of bladder tumour (TURBT) of large bladder tumours. METHODS: We queried our institution's billing data to identify patients who underwent TURBT for large bladder tumours >5cm (CPT 52240) by two urologists at an academic centre from January 2009 through April 2013. Only patients who underwent initial-staging TURBT for urothelial cancer were included. Pathological reports were reviewed for stage, number of separate pathological specimens per TURBT, and presence of cautery artifact. Operative reports were reviewed for whether additional cold cup biopsies were taken of other suspicious areas of the bladder, resident involvement, and type of electrocautery. RESULTS: We identified 119 patients who underwent initial staging TURBT for large tumours. Cautery artifact interfered with accurate staging in 7/119 (6%) of cases. Of these, six patients underwent restaging TURBT, with 50% percent experiencing upstaging to T2 disease. Tumour size, tumour grade, whether additional cold cup biopsies were taken, number of separate pathological specimens sent, and resident involvement were not associated with cautery artifact (all p>0.05). Bipolar resection had a higher rate of cautery artifact 5/42 (12%), compared to monopolar resection 2/77 (2.6%) approaching significance (p=0.095). CONCLUSIONS: Cautery artifact may delay accurate staging at initial TURBT for large tumours by understaging up to 6% of patients.

Suppression of ERß signaling via ERß knockout or antagonist protects against bladder cancer development.

Epidemiological studies showed that women have a lower bladder cancer (BCa) incidence, yet higher muscle-invasive rates than men, suggesting that estrogen and the estrogen receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERß), may play critical roles in BCa progression. Using in vitro cell lines and an in vivo carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced mouse BCa model, we found that ERß plays a positive role in promoting BCa progression. Knockdown of ERß with ERß-shRNA in ERß-positive human BCa J82, 647v and T24 cell lines led to suppressed cell growth and invasion. Mice lacking ERß have less cancer incidence with reduced expression of the proliferation marker Ki67 in BBN-induced BCa. Consistently, our results show that non-malignant urothelial cells with ERß knockdown are more resistant to carcinogen-induced malignant transformation. Mechanism dissection found that targeting ERß suppressed the expression of minichromosome maintenance complex component 5 (MCM5), a DNA replication licensing factor that is involved in tumor cell growth. Restoring MCM5 expression can partially reverse ERß knockdown-mediated growth reduction. Supportively, treating cells with the ERß-specific antagonist, 4-[2-Phenyl-5,7-bis(trifluoromethyl) pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP), reduced BCa cell growth and invasion, as well as MCM5 expression. Furthermore, we provide the first evidence that BCa burden and mortality can be controlled by PHTPP treatment in the carcinogen-induced BCa model. Together, these results demonstrate that ERß could play positive roles in promoting BCa progression via MCM5 regulation. Targeting ERß through ERß-shRNA, PHTPP or via downstream targets, such as MCM5, could serve as potential therapeutic approaches to battle BCa.

(Almost) painless surgery: a historical review of the evolution of intraurethral anesthesia in urology.

OBJECTIVE: The discovery of local anesthesia revolutionized urologic surgery. We investigate the evolution of intraurethral anesthesia in urologic surgery beginning in 1884. METHODS: A review of the literature was performed, reviewing the history of local anesthesia for urologic surgery, with a specific emphasis on intraurethral anesthesia. Using the University of Rochester libraries catalog "Voyager," a search was performed reviewing the primary literature published on intraurethral anesthesia beginning from 1884 through 2009. We also reviewed published literature in Ovid Med and PubMed for articles relevant to the topic of intraurethral anesthesia. The search terms were intraurethral, cocaine, lidocaine, and anesthesia. RESULTS: In the 1840s, it was demonstrated that ether, nitrous oxide, and chloroform could prevent the pain of surgery, resulting in a dramatic increase in surgery. At Massachusetts General Hospital between 1845 and 1847, surgeries increased 2.5-fold. Four decades later, it was demonstrated that cocaine allowed for adequate analgesia without the side effects of general anesthesia, resulting in a dramatic increase in urologic surgery. Cocaine was gradually replaced as an intraurethral anesthetic as safer local anesthetics, such as lidocaine, became introduced. Modern studies show conflicting results over the efficacy and ideal administration of intraurethral anesthetics. CONCLUSIONS: Local anesthesia was rapidly accepted by urologists around the world and used in a wide variety of urologic surgeries, contributing to the acceptance of anesthesia and a revolution of the practice of surgery. To this day, intraurethral anesthesia continues to be a widely used and effective technique in urology, although the ideal method of use is largely left up to individual preference.

Selective disruption of ER{alpha} DNA-binding activity alters uterine responsiveness to estradiol.

In vitro models have been used to demonstrate that estrogen receptors (ERs) can regulate estrogen-responsive genes either by directly interacting with estrogen-responsive element (ERE) DNA motifs or by interacting with other transcription factors such as AP1. In this study, we evaluated estrogen (E(2))-dependent uterine gene profiles by microarray in the KIKO mouse, an in vivo knock-in mouse model that lacks the DNA-binding function of ERalpha and is consequently restricted to non-ERE-mediated responses. The 2- or 24-h E(2)-mediated uterine gene responses were distinct in wild-type (WT), KIKO, and alphaERKO genotypes, indicating that unique sets of genes are regulated by ERE and non-ERE pathways. After 2 h E(2) treatment, 38% of the WT transcripts were also regulated in the KIKO, demonstrating that the tethered mechanism does operate in this in vivo model. Surprisingly, 1438 E(2)-regulated transcripts were unique in the KIKO mouse and were not seen in either WT or alphaERKO. Pathway analyses revealed that some canonical pathways, such as the Jak/Stat pathway, were affected in a similar manner by E(2) in WT and KIKO. In other cases, however, the WT and KIKO differed. One example is the Wnt/beta-catenin pathway; this pathway was impacted, but different members of the pathway were regulated by E(2) or were regulated in a different manner, consistent with differences in biological responses. In summary, this study provides a comprehensive analysis of uterine genes regulated by E(2) via ERE and non-ERE pathways.

Estrogen-induced proliferation of uterine epithelial cells is independent of estrogen receptor alpha binding to classical estrogen response elements.

Acting via the estrogen receptor (ER), estradiol exerts pleomorphic effects on the uterus, producing cyclical waves of cellular proliferation and differentiation in preparation for embryo implantation. In the classical pathway, the ER binds directly to an estrogen response element to activate or repress gene expression. However, emerging evidence supports the existence of nonclassical pathways in which the activated ER alters gene expression through protein-protein tethering with transcription factors such as c-Fos/c-Jun B (AP-1) and Sp1. In this report, we examined the relative roles of classical and nonclassical ER signaling in vivo by comparing the estrogen-dependent uterine response in mice that express wild-type ERalpha, a mutant ERalpha (E207A/G208A) that selectively lacks ERE binding, or ERalpha null. In the compound heterozygote (AA/-) female, the nonclassical allele (AA) was insufficient to mediate an acute uterotrophic response to 17beta-estradiol (E2). The uterine epithelial proliferative response to E2 and 4-hydroxytamoxifen was retained in the AA/-females, and uterine luminal epithelial height increased commensurate with the extent of ERalpha signaling. This proliferative response was confirmed by 5-bromo-2'-deoxyuridine incorporation. Microarray experiments identified cyclin-dependent kinase inhibitor 1A as a nonclassical pathway-responsive gene, and transient expression experiments using the cyclin-dependent kinase inhibitor 1A promoter confirmed transcriptional responses to the ERalpha (E207A/G208A) mutant. These results indicate that nonclassical ERalpha signaling is sufficient to restore luminal epithelial proliferation but not other estrogen-responsive events, such as fluid accumulation and hyperemia. We conclude that nonclassical pathway signaling via ERalpha plays a critical physiologic role in the uterine response to estrogen.

Paraffinoma of the urinary bladder.

We present a rare case of paraffinoma of the urinary bladder. Paraffinomas involving the urinary tract are rare and not well described. They are usually associated with insertion of materials into the lower urinary tract by patients with psychiatric disorders. Not only can the diagnosis be delayed, but they are also easily misdiagnosed. They are usually discovered during work up for recurrent urinary tract infections. Therefore, a high index of suspicion is needed in patients with recurrent urinary tract infections, psychiatric histories, and past history of foreign object insertion. Treatment options for paraffinoma includes open surgical excision, possibly transurethral excision or dissolution, and is usually dictated by the size of the mass.

Microsurgical varicocelectomy for infertile couples with advanced female age: natural history in the era of ART.

Varicocele represents the most common cause of male infertility, and most reports indicate that varicocelectomy has a beneficial effect on male fertility and pregnancy outcome. Assisted reproductive technologies (ARTs) are an alternative to varicocelectomy for the management of couples with a varicocele. The age of the female partner is important in the decision-making process; however, the true influence of female age on pregnancy outcome following varicocelectomy or ART in these couples is unknown. We evaluated the outcomes of 2 cohorts of infertile men with a varicocele and a female partner 35 years of age or older; one group selected varicocelectomy and the other a nonsurgical approach. We reviewed a group of consecutive infertile men who underwent microsurgical varicocelectomy and whose partners are 35 years of age or older (n = 110). We also reviewed a consecutive group of men with varicoceles who elected not to have surgery and whose partners are 35 years of age or older (n = 94). The outcome measures included changes in semen parameters, pregnancy rates (assisted and unassisted), and use of ART. The surgical and nonsurgical groups had comparable semen parameters and female ages. Mean sperm concentration and motility increased significantly after varicocelectomy (P < .05). At a mean of 30 months follow-up, 35% of couples in the surgical group achieved a spontaneous pregnancy and an additional 6% achieved a pregnancy via ART (20% of this group attempted ART). In the nonsurgical group, 25% achieved a spontaneous pregnancy and an additional 16% achieved a pregnancy with ART (40% of this group attempted ART). This study on the natural history of infertile men with varicocele and advanced female age suggests that the surgical and nonsurgical approaches offer comparable pregnancy outcome (combined assisted and unassisted pregnancy rates are about 40%). Overall, these data suggest that varicocelectomy is an acceptable option for couples with advanced female age, but other female factors must be considered in the decision-making process.

Should all urologists performing vasectomy reversals be able to perform vasoepididymostomies if required?

PURPOSE: While vasectomy reversal is a highly successful procedure 10% to 30% of reversals may fail. Despite the general consensus that an epididymal obstruction may occur following a vasectomy and that some men should undergo vasoepididymostomy (VE) rather than vasovasostomy (VV), the practice of many urologists in our region has been to offer only VV for vasectomy reversal. We examined the potential causes for vasectomy reversal failure in patients who had undergone VV without an attempt at VE. MATERIALS AND METHODS: We conducted a retrospective review of patients who had undergone redo vasectomy reversal from January 1999 to September 2001. A total of 22 patients underwent redo reversal with a minimum followup of 2 years. The medical records of all patients were then reviewed. Patients and partners seen postoperatively in the clinic were questioned regarding any pregnancy or deliveries. RESULTS: We examined 22 patients who had undergone redo vasectomy reversal. Of 22 patients 9 (40.9%) underwent repeat VV, 8 (36.3%) underwent bilateral VE for a presumed unrecognized epididymal obstruction and 5 (22.7%) had a combination of VE and VV. Of the 44 reproductive units studied 23 (52.3%) had a failed vasal anastomosis while 21 (47.7%) had an unrecognized epididymal obstruction. Based on semen analysis patency was observed in 75% of patients who had undergone vasovasostomy as a redo procedure. A patency rate of 60% was found in patients who underwent vasoepididymostomy and vasovasostomy unilaterally, and patency rates for bilateral VE were 63%. CONCLUSIONS: Our study indicates that a large proportion of men (48%) have an epididymal obstruction as the etiology for vasectomy reversal failure. We recommend that all surgeons offering vasectomy reversals be able to offer VE if required based on intraoperative findings to serve the patient adequately as well as his partner and their future fertility.

Does the gonadotropin-releasing hormone stimulation test predict clinical outcomes after microsurgical varicocelectomy?

OBJECTIVES: To examine the predictive value of the gonadotropin-releasing hormone (GnRH) stimulation test in a large cohort of infertile men undergoing varicocelectomy. METHODS: We examined the records of 144 consecutive infertile couples in whom the man underwent microsurgical varicocelectomy between September 1998 and December 2002. All men underwent a GnRH stimulation test before surgery. Data on the preoperative and postoperative semen parameters, pregnancy outcome, and follicle-stimulating hormone (FSH) and luteinizing hormone increase after GnRH stimulation were recorded. RESULTS: The mean (+/-SE) sperm concentration and motility 6 months after varicocelectomy were significantly greater than the preoperative values (25.3 +/- 2.4 versus 19.7 +/- 2.1 x 10(6)/mL and 29.2% +/- 1.4% versus 25.3% +/- 1.3%, respectively, P <0.05). Overall, 28% of the couples achieved a spontaneous pregnancy at a mean of 22 months of follow-up. The median elevation in the FSH and luteinizing hormone value 60 minutes after GnRH administration was 1.8 and 5.6 times the baseline level, respectively. No statistically significant relationship was found between the FSH or LH response to GnRH stimulation and improvement in the semen parameters or positive pregnancy outcome in our population. CONCLUSIONS: Our data showed that the FSH response to bolus GnRH stimulation does not predict improvement in semen parameters or unassisted pregnancy outcome in couples in whom the man undergoes varicocelectomy (for treatment of varicocele). The study was the largest of its type and sufficiently powered to validate these findings. The results indicate that the bolus GnRH stimulation test is of no clinical value in the treatment of infertile men with varicoceles.

The epididymal slide technique: a tension-free anastomosis in a vasoepididymostomy.

PURPOSE: Vasoepididymostomy is a technically demanding procedure that requires excellent positioning of the abdominal vas deferens at the epididymal tubule as well as a tension-free anastomosis. We describe a novel technique of securing the vas deferens to the testicle that allows manipulation of the epididymis and ensures a tension-free anastomosis. MATERIALS AND METHODS: After the vas deferens and epididymis are isolated in the usual fashion the vas is brought to the lateral portion of the testicle. A stay stitch is placed on the abdominal vas. This stay stitch is then placed through the tunica albuginea immediately posterior to the corpus or cauda epididymis. This allows the epididymis to slide in cephalad and caudad fashion prior to vasoepididymostomy and allows a tension-free anastomosis. RESULTS: We have used this technique routinely for vasoepididymostomy without any associated complications and have found it to be technically feasible in our last 50 cases. CONCLUSIONS: Although it is simple, the epididymal slide technique allows minimal to no distortion of the epididymal tubule, secure and safe fixation of the vas deferens, flexibility in choosing an appropriate epididymal tubule and tailoring of tension at the conclusion of the procedure. This technique is now used routinely at our center to allow a tension-free anastomosis during vasoepididymostomy and it has been technically feasible in all of our last 50 cases.